This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of the Multicenter AIDS Cohort Study (MACS is to elucidate the natural history of human immunodeficiency virus type 1 (HIV-1) infection in men who have sex with men, including: 1) the long term effectiveness, at the population level, of highly active antiretroviral therapy (HAART) and new therapies to which the MACS cohort will be exposed;2) the determinants of individual responses to HAART and the mechanisms of adverse effects of treatment, including side effects and development of drug resistance;3) characterization of virologic parameters (including antigenic and genetic factors), immune responses, and host genetic factors in progressors and non-progressors, especially as they can contribute to development of therapeutic vaccines;4) further characterization of the nature of resistance to infection in HIV-1 seronegative highly exposed subjects, especially as they relate to development of an effective preventive vaccine;5) increasing knowledge of prognostic markers of disease progression in a large cohort with varying use of therapies;6) determination of factors that contribute to specific outcomes of HIV-1 induced immunosuppression;7) further elucidation of the epidemiology and pathogenesis of HIV-1 related malignancies.